The first examples of "pre-aromatic" 1,2-dihydro-1,2-azaborine heterocycles have been structurally characterized, enabling the direct comparison of delocalized bonds of 1,2-dihydro-1,2-azaborines to their corresponding formal double and single bonds in nonaromatic systems. The crystallographic data provide an unprecedented look into the structural changes that occur in six-membered BN-heterocycles on their road to aromaticity, and they establish with little ambiguity that 1,2-dihydro-1,2-azaborines possess delocalized structures consistent with aromaticity.

The first general synthesis of boron-substituted 1,2-dihydro-1,2-azaborines is described. The versatile 1,2-dihydro-1,2-azaborine precursor 4 is synthesized through a ring-closing metathesis-oxidation sequence. Treatment of 4 with a wide range of anionic nucleophiles furnishes the desired adducts 5 in good yields. The scope includes hydrogen- and a variety of carbon- and heteroatom-based nucleophiles. Furthermore, the boron-containing isostere (7) of the potent hypolipidemic agent, methyl 2-ethylphenoxyacetate (8), is readily prepared through our method.

The protecting group-free synthesis of a versatile 1,2-azaborine synthon 5 is described. Previously inaccessible 1,2-azaborine derivatives, including the BN isostere of phenyl phenylacetate and BN1 triphenylmethane were prepared from 5 and characterized. The structural investigation of BN phenyl phenylacetate revealed the presence of a unique NH-carbonyl hydrogen bond that is not present in the corresponding carbonaceous analogue. The methyne CH in BN triphenylmethane was found to be less acidic than the corresponding proton in triphenylmethane. The gram-quantity synthesis of the parent 1,2-azaborine 4 was demonstrated, which enabled the characterization of its boiling point, density, refractive index, and its polarity on the ET(30) scale.

“Fused” BN indoles are an emerging class of boron-containing indole mimics, featuring similar geometric structure and electophilic aromatic substitution reactivity as indoles, however exhibiting distinct electronic structure, leading to unique optoelectronic properties. Herein we report the synthesis of the parent N-H BN indole, and provide a head-to-head comparison of the structural features, pKa values, and optoelectronic properties of this hybrid organic/inorganic indole with the classic natural indole.

Aromatic and single-olefin six-membered BN heterocycles were synthesized, and the heats of hydrogenation were measured calorimetrically. A comparison of the hydrogenation enthalpies of these compounds revealed that 1,2-azaborines have a resonance stabilization energy of 16.6 ± 1.3 kcal/mol, in good agreement with calculated values.

We present a comprehensive electronic structure analysis of two BN isosteres of indole using a combined UV-photoelectron spectroscopy (UV-PES)/computational chemistry approach. Gas-phase He I photoelectron spectra of external BN indole I and fused BN indole II have been recorded, assessed by density functional theory calculations, and compared with natural indole. The first ionization energies of these indoles are natural indole (7.9 eV), external BN indole I (7.9 eV), and fused BN indole II (8.05 eV). The computationally determined molecular dipole moments are in the order: natural indole (2.177 D) > fused BN indole II (1.512 D) > external BN indole I (0.543 D). The λmax in the UV–vis absorption spectra are in the order: fused BN indole II (292 nm) > external BN indole I (282 nm) > natural indole (270 nm). The observed relative electrophilic aromatic substitution reactivity of the investigated indoles with dimethyliminium chloride as the electrophile is as follows: fused BN indole II > natural indole > external BN indole I, and this trend correlates with the π-orbital coefficient at the 3-position. Nucleus-independent chemical shifts calculations show that the introduction of boron into an aromatic 6π-electron system leads to a reduction in aromaticity, presumably due to a stronger bond localization. Trends and conclusions from BN isosteres of simple monocyclic aromatic systems such as benzene and toluene are not necessarily translated to the bicyclic indole core. Thus, electronic structure consequences resulting from BN/CC isosterism will need to be evaluated individually from system to system.

We report the first examples of a "BN-fused" indole, and we demonstrate that this new family of unnatural indole derivatives undergoes electrophilic aromatic substitution (EAS) reactions with the same regioselectivity as its organic analogue. Competition experiments reveal that N-t-Bu-BNindole is more nucleophilic in EAS reactions than its carbonaceous counterpart. X-Ray structural analysis between BN indole and classic indole highlights significant differences in bond distances, in particular for bonds associated with the boron atom.Indole 1 is one of the most ubiquitous heterocyclic motifs in nature. Due to the abundance of biologically active indole derivatives, 2 the indole ring system has become an important structural component in drug discovery efforts. Consequently, the synthesis and functionalization of indoles has been a major focus in research, the expansion of the chemical space of accessible indole structures being one of the goals. 3 An alternative approach to expand structural diversity is "elemental isosterism". To this end, the BN/CC isosterism has recently emerged as a viable strategy to create biomimetic analogues of common structural units in organic molecules (e.g., olefin, 4 benzene, 5 and indene 6 ). Despite the recent advances in this area, the elemental isosterism of the biologically important indole has remained virtually unexplored. To date, the only BN-substituted indoles are phenylenediamine-type heterocycles containing an external BN unit as illustrated in 1 (Scheme 1). 7,8 To the best of our knowledge, electrophilic aromatic substitution (EAS), a crucial reaction of the biochemistry of indoles 9 has not been demonstrated with these phenylenediamine-type BN indoles. Herein we report the first example of a "BN-fused" indole (e.g., heterocycle 2 in Scheme 1), and we demonstrate that this new BN indole undergoes EAS reactions with the same regioselectivity as its organic analogue, N-t-Buindole 3. 10 Synthesis of N-t-Bu-BN-indole 2 begins with the condensation of N-t-Bu-N′-allylethylenediamine with in situ-generated allylboron dichloride (Scheme 2), affording heterocycle 4 in 50% yield. Ring-closing metathesis (RCM) with Grubbs first generation catalyst provides the bicyclic 5 in 51% yield. 11 The yield of the RCM step can be improved to 79% using Schrock's catalyst. Dehydrogenation of precursor 5 to furnish the target compound 2 is accomplished in the presence of Pd/C in refluxing decane. 12 With N-t-Bu-BN-indole 2 in hand, we then investigated its reactivity toward EAS. Indole itself displays high EAS reactivity, which is estimated to be orders of magnitude greater than benzene. 13 This is due to indole's electron-rich nature, and the high electron density at its 3-position is responsible for indole's regioselectivity toward EAS reactions. The bicyclic N-tBu-BN-indole 2 consists of a 6-membered 1,2-dihydro-1,2-azaborine heterocycle 14,15 and a lsy@uorgon.edu. Supporting Information Available. Experimental procedures and compound characterization data (PDF). This material is a...

Indole is a heterocycle of great importance to biological systems and materials applications. Synthesis of indole and its derivatives has been a major focus of research for over a century. BN/CC isosterism is an emerging strategy for expanding the structural diversity of indole-based compounds. Two classes of BN indoles have been reported to date: the well-studied “external” BN indoles (or 1,3,2-benzodiazaborolines), and the recently reported “fused” BN indoles. This perspective presents the history of both classes of indole isosteres, with a general overview of their synthesis, functionalization, and properties.